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Biomedical subjects

D D Braat

Publications and source records attributed to D D Braat.

At least 19 recordsLinked to original sources

Two cycles with single embryo transfer versus one cycle with double embryo transfer: a randomized controlled trial.

BACKGROUND: With the aim of reducing the number of multiple pregnancies after IVF we investigated the effectiveness of two cycles with single embryo transfer (SET) and one cycle with double embryo transfer (DET) after IVF and calculated the cost-effectiveness of both strategies. METHODS: A randomized controlled trial was performed in 107 women, aged <35 years, in their first IVF cycle, with at least one good quality embryo. They were randomized to the SET (n = 54) or DET (n = 53) group using a computer-generated random block number table, stratified for primary or secondary infertility. RESULTS: The cumulative live birth rates per woman randomized of two consecutive cycles of SET [41%; 95% confidence interval (CI) 27-54] versus one cycle of DET (36%; 95% CI 23-49) were comparable, whereas the multiple pregnancy rate was significantly higher: 37% (95% CI 15-59) in the DET and 0% in the in the SET group (P = 0.002). Combining the medical costs of the IVF treatments (where 1.5 more SET cycles were required to achieve each live birth) and of pregnancies up to 6 weeks after delivery, the total medical costs of DET per live birth were 13,680 and 13,438 for SET. CONCLUSIONS: Two cycles with SET were equally effective as one cycle with DET, and the medical costs per live birth up to 6 weeks after delivery were the same. However, if lifetime costs for severe handicaps are included, more than 7000 per live birth will be saved after implementing SET. Because of the high probability of multiple pregnancies in this group of IVF patients, only SET should be performed.

Adult↗

[A model code of practice in accordance with the Dutch Embryo act].

Under the terms of the Dutch Embryo Act, institutions that perform in vitro fertilisation must work in accordance with a legally prescribed procedure. A model protocol has been drawn up under the auspices of the Dutch Institute for Healthcare Improvement that can serve as a guideline and that may be amplified in details with regard to local circumstances. In vitro fertilisation is reserved to licensed centres with expert and experienced personnel. These centres must fulfil specific standards for both the clinical part and the laboratory part of the treatment. The decision in favour of ovarian stimulation depends on the wish to be able to select from multiple embryos and must be weighed against the burden on the patient, her age and the risk of developing an ovarian hyperstimulation syndrome. Placing more than two embryos at a time is discouraged. In the contract between the depositors and the depository concerning the storage of embryos (cryopreservation), the points of departure are that the parties involved must agree on the use of the embryos and that each involved person may withdraw his or her permission at any time. In the Netherlands, oocyte donation is performed predominantly in women with premature ovarian failure. The maximum age of the acceptor is 45 years. Legally, the minimum age of a donor is 18 years, but the Committee recommends caution with donors under the age of 30 years; from the point of view of treatment efficacy, the maximum age is 40 years. For each individual oocyte donation procedure, permission is required from the medical-ethical assessment committee of the hospital in question. Often, a written report to the committee from the treating gynaecologist and a psychosocial counsellor will suffice. Because of the increased risk of pregnancy complications after oocyte donation, control and delivery in hospital are recommended. Post-mortem use of gametes or embryos is permitted, provided that the parties involved have given written permission.

Adult↗

[Obstructive azoospermia in men who wish to father children; diagnosis and surgical sperm retrieval].

OBJECTIVE: To evaluate diagnostic procedures and surgical sperm retrieval in men with suspected obstructive azoospermia who wish to father children. DESIGN: Descriptive, retrospective. METHOD: During the period 1 April 1999-31 December 2001 93 men suspected of having obstructive azoospermia underwent surgical sperm retrieval by means of percutaneous epididymal sperm aspiration (PESA). In each patient a testicular biopsy was performed to determine the Johnsen score (a score > or = 8 is equivalent to a normal spermatogenesis). Cryopreservation was performed whenever possible. The findings in both percutaneous and surgical sperm retrieval were compared. RESULTS: In 76 patients (82%) epididymal motile sperm were obtained using PESA. Their Johnsen score on the testis biopsy was 9.1 (range: 7.4-10). In 73 of the patients the Johnsen score was > or = 8. In the 17 patients (18%) in whom no sperm were found with PESA, the median Johnsen score was 5.8 (range: 2-9.8). Epididymal sperm were not found in patients with a testicular volume < 15 ml. In all 28 patients who had undergone a vasectomy in the past, motile sperm were found along with a Johnsen score > or = 8. In 23 of the 24 patients with congenital bilateral absence of the vas deferens (CABVD) the Johnsen score was > or = 8. Cryopreservation was possible in 45 (59%) of all patients and in 5 (35%) of the 13 patients with an unknown cause for the obstructive azoospermia. CONCLUSION: In men with suspected obstructive azoospermia in whom sperm were found using PESA, a diagnostic testis biopsy provided no additional relevant information about the spermatogenesis. There was always a good spermatogenesis after vasectomy. CBAVD patients probably had at least some focal areas in the testes with normal spermatogenesis. Sperm retrieval and cryopreservation could be carried out less frequently in the case of obstructions with an unknown cause.

Adult↗

[Obstructive azoospermia in men who wish to father children; initial clinical results of intracytoplasmatic sperm injection (ICSI) with surgically retrieved epididymal semen].

OBJECTIVE: To evaluate the results of intracytoplasmatic sperm injection (ICSI) with surgically retrieved epididymal semen. DESIGN: Prospective, descriptive. METHODS: Patients with an obstructive azoospermia confirmed by cytological examination of a testis biopsy, and conforming to the regular IVF/ICSI criteria as laid down in 2001 at the University Medical Centre St Radboud Nijmegen, the Netherlands, were included for percutaneous epididymal sperm aspiration (PESA) and ICSI. The main outcome measure was the ongoing pregnancy rate per initiated cycle. RESULTS: A total of 44 cycles were started in 31 couples. In 43 cases (98%) an ovum pick-up was performed and 41 (93%) embryo transfers were carried out. In 19 (43%) cases, treatment resulted in a positive pregnancy test and 15 (34%) ongoing pregnancies were recorded. In total, 17 healthy children were born (11 boys and 6 girls). CONCLUSION: ICSI with surgically retrieved semen was successfully used as a treatment for childlessness caused by obstructive azoospermia.

Adult↗

[Multiple pregnancies: epidemiology and management].

Since the 1980s, the percentage of multiple pregnancies in the Netherlands has increased. Nowadays, the percentage of triplets is decreasing but there is still an increase in the percentage of twin pregnancies. A major cause is that Dutch women tend to delay starting a family until an advanced age. This increases their chances of a spontaneous multiple pregnancy. Moreover, they are prone to subfertility and consequently have a greater chance of undergoing treatments involving assisted-reproduction techniques such as intra-uterine insemination (IUI) and in-vitro fertilisation. In the Netherlands, the majority of higher order multiple pregnancies result from mild ovarian hyperstimulation in combination with IUI. In case of in-vitro fertilisation, since the practice of transferring a maximum of two embryos still results in 20-25% twin pregnancies, single-embryo transfer should be advocated more often.

Adult↗

Dynamics of immunoreactive endothelin plasma levels during ovarian stimulation for in vitro fertilization with and without dietary sodium restriction.

OBJECTIVE: To investigate the correlation between immunoreactive endothelin plasma levels and both the number and size of follicles and its relationship with the development of ovarian hyperstimulation syndrome, in in vitro fertilization cycles, with and without dietary sodium restriction. STUDY DESIGN: Randomized study in an assisted reproduction unit of a large teaching hospital. Data of 88 women form the basis of this report (45 ad libitum sodium intake and 43 dietary sodium restriction). Non-parametric tests were used for statistical analysis. RESULTS: Immunoreactive endothelin plasma levels neither correlate with the number of follicles, independent of their size, nor with the grade of ovarian hyperstimulation syndrome. Immunoreactive endothelin plasma levels decrease significantly in the luteal phase. These results are the same in both sodium diet groups. CONCLUSIONS: Immunoreactive endothelin plasma levels do not correlate with the number and size of follicles and they are not related to the development of ovarian hyperstimulation syndrome. These findings are independent of sodium intake.

Diet, Sodium-Restricted↗

Coeliac disease and reproductive disorders: a neglected association.

Coeliac disease is a chronic disease caused by a permanent intolerance to ingested gluten resulting in immunologically mediated inflammatory damage of the small-intestinal mucosa. The wide spectrum of clinical symptoms is partly due to the malnourished state caused by the malabsorption of macro- and micronutrients. Fertility problems, sexual dysfunction and obstetrical complications are more frequently observed in patients with coeliac disease. These reproductive disorders may be a consequence of the endocrine derangements caused by selective nutrient deficiencies. Nowadays, the early diagnosis and treatment of coeliac disease is possible and not very costly. Therefore, coeliac disease must be seriously considered in the preconceptional screening and treatment of patients with reproductive disorders.

Celiac Disease↗

DAZLA: an important candidate gene in male subfertility?

PURPOSE: To study the role of the autosomal candidate gene DAZLA (Deleted in AZoospermia Like Autosome) in male subfertility. METHODS: We reviewed clinical data of subfertile men with oligozoospermia or azoospermia, mostly candidates for intracytoplasmic sperm injection (ICSI). Mutation detection was performed using polymerase chain reaction followed by single strand conformation polymorphism analysis. All shifted bands were analyzed by sequencing. RESULTS: We searched for mutations in 44 subfertile men. Nine subfertile men were included, because family history showed that their brothers also faced fertility problems. In these men a possible autosomal gene defect may contribute to their fertility problem. No mutations were found, except for two polymorphisms in intron 4 and 5. CONCLUSION: At this moment it does not seem relevant to search for possible mutations in the DAZLA gene in clinical practice.

DNA Mutational Analysis↗

Decreased fertilization rate and embryo quality after ICSI in oligozoospermic men with microdeletions in the azoospermia factor c region of the Y chromosome.

Microdeletions of the azoospermia factor (AZF) region of the Y chromosome occur in between 1 and 29% of oligozoospermic and azoospermic men, and most deletions are found in the AZFc region. These men can father children when intracytoplasmic sperm injection (ICSI) is used, but the success rate is unclear. Thus, the success rate of 19 ICSI treatments in eight couples with a microdeletion in the AZFc region of the Y chromosome was analysed retrospectively. These were compared with a control group of 239 ICSI treatments in 107 couples undergoing ICSI treatment with ejaculated spermatozoa. The fertilization rate was significantly lower in the group of Y-deleted men (55%; 95% CI: 41-69%) compared with controls (71%; 95% CI: 67-74%; P < 0.01). The embryo quality was also significantly poorer among Y-deleted men (P<0.001). Pregnancy, implantation and take-home baby rates were not significantly lower in the Y-deleted group. This study shows that ICSI in oligozoospermic men with microdeletions in the AZFc region of the Y chromosome leads to a lower fertilization rate and poorer embryo quality.

Adult↗

Increased serum FSH in female fragile X premutation carriers with either regular menstrual cycles or on oral contraceptives.

Fragile X premutations are known to be a risk factor for diminished ovarian function at a relatively young age. We studied endocrine profiles of female fragile X family members (n = 79) at risk of premature ovarian failure (POF). Of these 79 women aged <40 years, 45 had menstrual cycles, and 34 were using oral contraceptives. Of the women with menstrual cycles, the premutation carriers had higher serum FSH concentrations than women who were not carrying the premutation. Even premutation carriers with regular cycles showed increased serum FSH concentrations. Moreover, premutation carriers using oral contraceptives also demonstrated increased serum FSH concentrations. Irrespective of whether oral contraceptives were used, a serum FSH concentration of > or =15 IU/l was more common in the premutation carriers than in the other women. One premutation carrier using oral contraceptives had a serum FSH concentration of >40 IU/l, the threshold that defines POF. We confirmed that premutation carriers with menstrual cycles demonstrate premature ovarian dysfunction. However, we also found endocrine signs of unrecognized ovarian dysfunction in premutation carriers using oral contraceptives, despite endocrine alterations by oral contraceptives. Premutation carriers may have a poorer prognosis for future pregnancy, either achieved spontaneously or by assisted reproductive technology. We recommend that premutation carriers should be counselled not to wait too long if they wish to start a family.

Adult↗

The effect of anxiety and depression on the outcome of in-vitro fertilization.

BACKGROUND: The study aim was to clarify the role of anxiety and depression on the outcome in assisted reproductive treatment. Previous studies on this topic have shown contradicting results, which may have been caused by population characteristics, the design of the study, or small sample sizes. METHODS: In a multicentre prospective study, 291 out of 359 (81%) consecutively invited women agreed to participate. Before down-regulation by means of gonadotrophin-releasing hormone (GnRH) analogues in a long IVF protocol, patients were asked to complete the Dutch version of the State and Trait Anxiety Inventory to measure anxiety, and the Dutch version of the Beck Depression Inventory (BDI) to measure depression. Multiple logistic regression analysis was used to analyse known predictors of pregnancy and psychological factors and their relationship with treatment outcome. RESULTS: A significant relationship was shown between baseline psychological factors and the probability to become pregnant after IVF/intracytoplasmic sperm injection (ICSI) treatment, controlling for other factors. State anxiety had a slightly stronger correlation (P = 0.01) with treatment outcome than depression (P = 0.03). CONCLUSIONS: Pre-existing psychological factors are independently related to treatment outcome in IVF/ICSI, and should therefore be taken into account in patient counselling. Psychological factors may be improved by intervention, whereas demographic and gynaecological factors cannot. Future studies should be directed towards underlying mechanisms involved and the role of evidence-based distress reduction in order to improve treatment results.

Adult↗

Psychological impact of preconception counseling: assessment of anxiety before and during pregnancy.

OBJECTIVE: Assessment of anxiety levels in women and men before and after preconception counseling and during the first trimester of pregnancy. METHODS: Couples were recruited from the fertility clinic of the University Medical Center Nijmegen, the Netherlands. Anxiety was assessed using the 40-item Spielberger State-Trait Anxiety Inventory (STAI). RESULTS: 53 women and 51 men (74%) completed the STAI both before and after counseling. Anxiety levels did not change significantly after counseling or during the first trimester of pregnancy. 83.4% would recommend preconception counseling to others. CONCLUSION: Preconception counseling is valued by the majority of women and men and does not lead to adverse psychological effects.

Journal Article↗

[Can a woman become pregnant after a stem cell transplantation?].

Three women with chronic myelogenous leukaemia underwent stem cell transplantation. They all were concerned about their future fertility. The first woman underwent egg donation when she was in complete remission, and gave birth to a healthy son. The second one underwent an IVF treatment before stem cell transplantation: 15 embryos were frozen. The third woman asked for cryopreservation of ovarian tissue. This procedure is not (yet) possible in our clinic. The possibilities and complications of these three procedures are discussed as well as the indication for the possible cryopreservation of ovarian tissue.

Adult↗

[Cryopreservation of ovarian tissue; now is the time for ethical considerations].

The development of ovarian tissue cryopreservation will expand the range of clinical applications in reproductive medicine. This emerging technology may have beneficial opportunities for patients, particularly in oncology, as well as for the process of oocyte donation. However, it will also lead to new moral problems requiring critical reflection concerning the criteria for tissue banking and future clinical applications. Because cryopreservation of ovarian tissue nowadays is the focus of experimental research, technology assessment is currently appropriate, anticipating introduction into clinical practice. Specific guidelines, developed by the medical profession in cooperation with ethicists and lawyers can contribute to prudent clinical use.

Cryopreservation↗

Imprinting effect in premature ovarian failure confined to paternally inherited fragile X premutations.

Fragile X premutations are considered to be a risk factor for premature ovarian failure (POF), which is usually defined as menopause at age <40 years. Since premutations may be inherited from either the mother or the father, we evaluated the influence of the inheritance pattern on the duration of reproductive life in female carriers. The occurrence of POF and age at menopause in women with a paternally inherited fragile X premutation (PIP) were compared to those in women with a maternally inherited fragile X premutation (MIP). We identified 148 women in whom the parental origin of the premutation could be determined. In 109 of these women we were able to establish whether POF had occurred: 82 women had a PIP, and 27 had a MIP. Twenty-three of the women (28%) with a PIP had POF, versus only 1 (3.7%) with a MIP (two -tailed Fisher's exact test; P=. 007). Kaplan-Meier analysis of all 148 premutations showed that the age at menopause was significantly lower in the women with a PIP than in the woman with a MIP (Breslow test in Kaplan-Meier analysis; P=.003). Our data strongly suggest that, when POF occurs in fragile X premutation carriers, a considerable proportion of the premutations are inherited paternally (parent-of-origin effect). We hypothesize that this may be owing to a paternal genomic imprinting effect.

Adult↗

Cumulative probability of achieving an ongoing pregnancy after in-vitro fertilization and intracytoplasmic sperm injection according to a woman's age, subfertility diagnosis and primary or secondary subfertility.

The aim of this study was to estimate reliable cumulative probabilities of achieving an ongoing pregnancy after successive in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) cycles, according to a woman's age, subfertility diagnosis and primary or secondary subfertility. Therefore reasons for quitting treatment without achieving an ongoing pregnancy were taken into account. Moreover, we studied whether there were trends in cumulative probabilities after adjustment for potential confounding effects of the other two characteristics, duration of subfertility, year of first treatment and reason for quitting treatment. In total, 2984 IVF/ICSI cycles were performed in 1315 couples at the University Hospital Nijmegen, The Netherlands, between 1991 and 1998. The 'realistic' cumulative probability of achieving an ongoing pregnancy was 54.5% after five consecutive IVF/ICSI cycles, which was about 10% lower (absolute value) than the optimistic probability calculated by life-table analysis and about 10% higher (absolute value) than the most pessimistic estimate. Women of 35 years or younger had a higher probability of achieving an ongoing pregnancy than the older women. As ICSI is now an option, there were no obvious differences between the subfertility diagnosis subgroups. The cumulative probability after the first two IVF/ICSI cycles was higher in women with secondary subfertility than in those with primary subfertility; this advantage disappeared after further treatment. These trends remained valid after adjustment for confounding factors.

Adult↗

Increasing the daily dose of recombinant follicle stimulating hormone (Puregon) does not compensate for the age-related decline in retrievable oocytes after ovarian stimulation.

A prospective, randomized, double-blind, multicentre (n = 6) study was conducted to compare the influence of either a 150 or 250 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH, Puregon) on the number of oocytes retrieved and the total dose used in down-regulated women between 30 and 39 years of age undergoing ovarian stimulation. In all, 138 women were treated with recombinant FSH, 67 with 150 IU and 71 with 250 IU. The number of oocytes retrieved in the low-dose group was 9.1 compared to 10.6 in the high-dose group (not significant). In the 30-33 years of age class receiving the 250 IU dose, a surplus of 4.2 oocytes (14.8 versus 10.6) was found, whereas in the 37-39 age class nearly one oocyte more was retrieved in the 150 IU group (8.1 versus 7.4). The total dose used to reach the criterion for human chorionic gonadotrophin (HCG) administration was 1727 IU for the women treated with 150 IU daily and 2701 IU for the 250 IU treated women (P < 0. 001). No significant relationships were found between serum FSH concentrations as obtained in the early follicular phase and the number of oocytes collected, or the total dose. It is concluded that in women between 30 and 39 years of age, the decline in number of oocytes retrieved with increasing age cannot be overcome by augmenting the daily dose of recombinant FSH from 150 to 250 IU.

Adult↗

External validation of the templeton model for predicting success after IVF.

This study aimed to externally validate the prognostic model presented by Templeton in 1996 for live births resulting from IVF treatment. Data were used from the University Hospital, Nijmegen, The Netherlands, from March 1991 to January 1999. The predictive capacity of the model in our population discriminated between those women with a low probability of success and those with a relatively high probability. Despite these encouraging findings, our data show that implementation of the model in clinical decision-making remains difficult. The Templeton model is not applicable or usable in daily clinical practice, because the model did not give more information about the prognosis for the vast majority of the patients. Therefore, the search for better prognostic factors resulting in better predictive models should continue.

Adult↗